avosentan and Proteinuria

avosentan has been researched along with Proteinuria* in 4 studies

Reviews

1 review(s) available for avosentan and Proteinuria

ArticleYear
Endothelin antagonism and reversal of proteinuric renal disease in humans.
    Contributions to nephrology, 2011, Volume: 172

    Endothelin (ET)-1 is a powerful mitogen and vasoconstrictor that contributes to cardiovascular and renal pathologies. In the kidney, ET causes vasoconstriction, sodium retention, mesangial cell inflammation and proliferation, hypertrophy of glomerular capillaries, and podocyte injury. The latter, due to destruction of the glomerular filtration barrier, is a key factor for renal protein loss. Experimental and recent clinical studies suggest that orally active drugs inhibiting ET(A) receptors are capable of not only inhibiting the progression, but also reversing glomerulosclerosis-related renal injury. Clinical studies using ET receptor antagonists (ERAs) have found regression of proteinuria which serves as a functional indicator of glomerular filtration barrier injury. The effects of ERA therapy can be observed in the presence of inhibition of the renin-angiotensin system, suggesting arenin-angiotensin system-independent therapeutic effect of ERAs. Thus, ET blockade is not an 'add-on' treatment, but represents an independent therapeutic principle. This article will discuss the underlying mechanisms of the antiproteinuric effects of ET antagonists, and summarize recent clinical trials in the field and the therapeutic potential of the ERA class of drugs for renal medicine.

    Topics: Endothelins; Humans; Isoxazoles; Kidney Diseases; Phenylpropionates; Proteinuria; Pyridines; Pyrimidines; Receptor, Endothelin A; Thiophenes

2011

Trials

1 trial(s) available for avosentan and Proteinuria

ArticleYear
Avosentan for overt diabetic nephropathy.
    Journal of the American Society of Nephrology : JASN, 2010, Volume: 21, Issue:3

    In the short term, the endothelin antagonist avosentan reduces proteinuria, but whether this translates to protection from progressive loss of renal function is unknown. We examined the effects of avosentan on progression of overt diabetic nephropathy in a multicenter, multinational, double-blind, placebo-controlled trial. We randomly assigned 1392 participants with type 2 diabetes to oral avosentan (25 or 50 mg) or placebo in addition to continued angiotensin-converting enzyme inhibition and/or angiotensin receptor blockade. The composite primary outcome was the time to doubling of serum creatinine, ESRD, or death. Secondary outcomes included changes in albumin-to-creatinine ratio (ACR) and cardiovascular outcomes. We terminated the trial prematurely after a median follow-up of 4 months (maximum 16 months) because of an excess of cardiovascular events with avosentan. We did not detect a difference in the frequency of the primary outcome between groups. Avosentan significantly reduced ACR: In patients who were treated with avosentan 25 mg/d, 50 mg/d, and placebo, the median reduction in ACR was 44.3, 49.3, and 9.7%, respectively. Adverse events led to discontinuation of trial medication significantly more often for avosentan than for placebo (19.6 and 18.2 versus 11.5% for placebo), dominated by fluid overload and congestive heart failure; death occurred in 21 (4.6%; P = 0.225), 17 (3.6%; P = 0.194), and 12 (2.6%), respectively. In conclusion, avosentan reduces albuminuria when added to standard treatment in people with type 2 diabetes and overt nephropathy but induces significant fluid overload and congestive heart failure.

    Topics: Aged; Blood Pressure; Body Weight; Diabetic Nephropathies; Disease Progression; Endothelins; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Pyridines; Pyrimidines; Treatment Outcome; Water-Electrolyte Imbalance

2010

Other Studies

2 other study(ies) available for avosentan and Proteinuria

ArticleYear
Endothelin antagonist as add-on treatment for proteinuria in diabetic nephropathy: is there light at the end of the tunnel?
    Journal of the American Society of Nephrology : JASN, 2011, Volume: 22, Issue:4

    Topics: Albuminuria; Atrasentan; Diabetic Nephropathies; Endothelins; Glomerular Filtration Rate; Humans; Proteinuria; Pyridines; Pyrimidines; Pyrrolidines; Renin-Angiotensin System; Treatment Outcome

2011
Endothelin receptor antagonists in proteinuric renal disease: every rose has its thorn.
    Journal of the American Society of Nephrology : JASN, 2010, Volume: 21, Issue:3

    Topics: Animals; Endothelin Receptor Antagonists; Humans; Proteinuria; Pyridines; Pyrimidines; Receptors, Endothelin

2010